Medicine and Health Sciences Commons^™

From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xinquan Wang, Sulan Luo

School of Veterinary and Biomedical Sciences: Faculty Publications

Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking …

On And Off Retinal Ganglion Cells Differentially Regulate Serotonergic And Gabaergic Activity In The Dorsal Raphe Nucleus, Ting Zhang, Lu Huang, Li Zhang, Minjie Tan, Mingliang Pu, Gary E. Pickard, Kwok -Fai So, Chaoran Ren

School of Veterinary and Biomedical Sciences: Faculty Publications

The dorsal raphe nucleus (DRN), the major source of serotonergic input to the forebrain, receives excitatory input from the retina that can modulate serotonin levels and depressive-like behavior. In the Mongolian gerbil, retinal ganglion cells (RGCs) with alpha-like morphological and Y-like physiological properties innervate the DRN with ON DRN-projecting RGCs out numbering OFF DRN-projecting RGCs. The DRN neurons targeted by ON and OFF RGCs are unknown. To explore retino-raphe anatomical organization, retinal afferents labeled with Cholera toxin B were examined for association with the postsynaptic protein PSD-95. Synaptic associations between retinal afferents and DRN serotonergic and GABAergic neurons were observed. …

Erratum To: Association Of Autophagy In The Cell Death Mediated By Dihydrotestosterone In Autoreactive T Cells Independent Of Antigenic Stimulation, Ting Jia, Anandhan Annadurai, Chandirasegara Massilamany, Rajkumar A. Rajasekaran, Rodrigo Franco, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

No abstract provided.

The Mechanistic Basis Of Hemoglobin Adaptation In The High-Flying Barheaded Goose: Insights From Ancestral Protein Resurrection, Chandrasekhar Natarajan, Amit Kumar, Hideaki Moriyama, Roy E. Weber, Angela Fago, Jay F. Storz

School of Veterinary and Biomedical Sciences: Faculty Publications

The bar-headed goose (‘BHG’, Anser indicus) is renowned for its trans-Himalayan migratory flights, and the elevated hemoglobin (Hb)-O2 affinity of this species is thought to make a key contribution to its capacity for powered flight at elevations of ~9000 m. Here we revisit the molecular basis of this text-book example of biochemical adaptation. Previous hypotheses about the molecular basis of the evolved increase in Hb-O2 affinity were tested by engineering BHGspecific mutations into recombinant human Hb. This approach can provide important insights, but one problem with such ‘horizontal’ comparisons – swapping residues between proteins of contemporary species – is that …

Complete Genome Sequence Of Highly Virulent Porcine Reproductive And Respiratory Syndrome Virus Variants That Recently Emerged In The United States, Aspen M. Workman, Timothy P.L. Smith, Fernando A. Osorio, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

A recent outbreak of particularly virulent disease caused by porcine reproductive and respiratory syndrome virus has occurred in swine herds across the United States. We report here the complete genome sequence of eight viral isolates from four Nebraska herds experiencing an outbreak of severe disease in 2016.

Kaposi’S Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (Myd88) Expression Via Modulation Of Its Rna, Amy Lingel, Erica Ehlers, Qianli Wang, Mingxia Cao, Charles Wood, Rongtuan Lin, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of …

Domain I Of The 5′ Non-Translated Genomic Region In Coxsackievirus B3 Rna Is Not Required For Productive Replication, L. Jaramillo, S. Smithee, S. Tracy, N. M. Chapman

Nebraska Center for Virology: Faculty Publications

Domain I is a cloverleaf-like secondary structure at the 5′ termini of all enterovirus genomes, comprising part of a cis-acting replication element essential for efficient enteroviral replication. 5′ genomic terminal deletions up to as much as 55% of domain I can occur without lethality following coxsackie B virus infections. We report here that the entire CVB structural domain I can be deleted without lethality.

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses, Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R. Pease, Richard J. Webby, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Head-to-head comparisons of conventional influenza vaccines with ade- novirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we de- veloped “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than …

Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5- fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. …

Noninvasive Assessment Of Cardiac Abnormalities In Experimental Autoimmune Myocarditis By Magnetic Resonance Microscopy Imaging In The Mouse, Chandirasegaran Massilamany, Vahid Khalilzad-Sharghi, Arunakumar Gangaplara, David Steffen, Shadi F. Othman, Jay Reddy

Jay Reddy Publications

Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice …

Sequence-Based Methods For Detecting And Evaluating The Human Gut Mycobiome, Mallory J. Suhr, Nabaraj Banjara, Heather E. Hallen-Adams

Department of Food Science and Technology: Faculty Publications

We surveyed the fungal microbiota in 16 fecal samples from healthy humans with a vegetarian diet. Fungi were identified using molecular cloning, 454 pyrosequencing and a Luminex analyte specific reagent (ASR) assay, all targeting the ITS region of the rRNA genes. Fungi were detected in each fecal sample and at least 46 distinct fungal operational taxonomic units (OTUs) were detected, from two phyla — Ascomycota and Basidiomycota. Fusarium was the most abundant genus, followed by Malassezia, Penicillium, Aspergillus, and Candida. Commonly detected fungi such as Aspergillus and Penicillium, as well as known dietary fungi Agaricus bisporus and …

Echinococcus Multilocularis In Foxes And Raccoon Dogs: An Increasing Concern For Baltic Countries, Guna Bagrade, Gunita Deksne, Zanda Ozoliņa, Samantha Jane Howlett, Maria Interisano, Adriano Casulli, Edoardo Pozio

Harold W. Manter Laboratory: Library Materials

Background

In Europe, the life cycle of Echinococcus multilocularis is predominantly sylvatic, involving red foxes (Vulpes vulpes) as the main definitive hosts and rodents such as muskrats and arvicolids as intermediate hosts. The parasite is the etiological agent of human alveolar echinococcosis, a malignant zoonotic disease caused by the accidental ingestion of eggs shed by definitive hosts in their feces. The aims of this study were to investigate the prevalence of E. multilocularis in red foxes and raccoon dogs (Nyctereutes procyonoides) and to study the environmental factors favoring the perpetuation of the parasite in Latvia. …

Student Absenteeism And The Comparisons Of Two Sampling Procedures For Culturable Bioaerosol Measurement In Classrooms With And Without Upper Room Ultraviolet Germicidal Irradiation Devices, Chunxiao Su, Josephine Lau, Shawn G. Gibbs

Durham School of Architectural Engineering and Construction: Faculty Publications

Upper room ultraviolet germicidal irradiance (UVGI) has been shown to reduce the concentration of bioaerosols in controlled chambers. However, there is a lack of experimental results on the reduction of bioaerosol concentrations by UVGI devices in actual uncontrolled buildings. This study was carried out in an American elementary school in the Midwest. Two sampling procedures were carried out in six selected classrooms with similar dimensions that were separated into two groups: (1) UVGI exposure group and (2) non-UVGI control group. Two-stage Tisch culturable impactors were utilized to collect airborne culturable bacteria and fungi. Monthly samples were collected during unoccupied period …

Reasons For Tubal Sterilisation, Regret And Depressive Symptoms, Karina M. Shreffler, Arthur L. Greil, Julia Mcquillan, Kami L. Gallus

Department of Sociology: Faculty Publications

Objective—To examine the associations between sterilisation reasons, regret, and depressive symptoms.

Study Design—Black, Hispanic, and non-Hispanic White US women ages 25–45 who participated in the National Survey of Fertility Barriers (NSFB) and reported a tubal sterilisation surgery were included in the sample for this study (n=837). Logistic regression was used to examine how characteristics of the sterilisation surgery (reasons for sterilisation, time since sterilisation, and new relationship since sterilisation) are associated with the odds of sterilisation regret, and linear regression was used to examine associations between sterilisation regret, sociodemographic factors, and depressive symptoms.

Results—Findings revealed that 28 …

Suppression Of Nlrp3 Inflammasome By Γ-Tocotrienol Ameliorates Type 2 Diabetes, Yongeun Kim, Wei Wang, Meshail Okla, Inhae Kang, Regis Moreau, Soonkyu Chung

Department of Nutrition and Health Sciences: Faculty Publications

The Nod-like receptor 3 (NLRP3) inflammasome is an intracellular sensor that sets off the innate immune system in response to microbial-derived and endogenous metabolic danger signals. We previously reported that γ-tocotrienol (γT3) attenuated adipose tissue inflammation and insulin resistance in diet-induced obesity, but the underlying mechanism remained elusive. Here, we investigated the effects of γT3 on NLRP3 inflammasome activation and attendant consequences on type 2 diabetes. γT3 repressed inflammasome activation, caspase-1 cleavage, and interleukin (IL) 1β secretion in murine macrophages, implicating the inhibition of NLRP3 inflammasome in the anti-inflammatory and antipyroptotic properties of γT3. Furthermore, supplementation of leptin-receptor KO mice …

Disparities In Access To Preventive Health Care Services Among Insured Children In A Cross Sectional Study, Christian King

Department of Nutrition and Health Sciences: Faculty Publications

Children with insurance have better access to care and health outcomes if their parents also have insurance. However, little is known about whether the type of parental insurance matters. This study attempts to determine whether the type of parental insurance affects the access to health care services of children. I used data from the 2009–2013 Medical Expenditure Panel Survey and estimated multivariate logistic regressions (N=26,152). I estimated how family insurance coverage affects the probability that children have a usual source of care, well-child visits in the past year, unmet medical and prescription needs, less than 1 dental visit per year, …

Creating A Community Of Practice To Prevent Suicide Through Multiple Channels: Describing The Theoretical Foundations And Structured Learning Of Pc Cares, Lisa Wexler, Diane Mceachern, Gloria Difulvio, Cristine Smith, Louis F. Graham, Kirk Dombrowski

Department of Sociology: Faculty Publications

It is critical to develop practical, effective, ecological, and decolonizing approaches to indigenous suicide prevention and health promotion for the North American communities. The youth suicide rates in predominantly indigenous small, rural, and remote Northern communities are unacceptably high. This health disparity, however, is fairly recent, occurring over the last 50 to 100 years as communities experienced forced social, economic, and political change and intergenerational trauma. These conditions increase suicide risk and can reduce people’s access to shared protective factors and processes. In this context, it is imperative that suicide prevention includes—at its heart— decolonization, while also utilizing the “best …

Test–Retest, Retest, And Retest: Growth Curve Models Of Repeat Testing With Immediate Post-Concussion Assessment And Cognitive Testing (Impact), Arthur C. Maerlender, Caitlin J. Masterson, Tiffany D. James, Jonathan Beckwith, Per Gunner Brolinson, Joe Crisco, Stefan Duma, Laura A. Flashman, Rick Greenwald, Steven Rowson, Beth Wilcox, Tom W. Mcallister

Department of Psychology: Faculty Publications

Computerized neuropsychological testing has become an important tool in the identification and management of sports-related concussions; however, the psychometric effect of repeat testing has not been studied extensively beyond test–retest statistics. The current study analyzed data from Division I collegiate athletes who completed Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) baseline assessments at four sequential time points that varied over the course of their athletic careers. Administrations were part of a larger National Institutes of Health (NIH) study. Growth curve modeling showed that the two memory composite scores increased significantly with successive administrations: Change in Verbal Memory was best represented …

Perceived Threat Associated With Police Officers And Black Men Predicts Support For Policing Policy Reform, Allison L. Skinner, Ingrid J. Haas

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Racial disparities in policing and recent high-profile incidents resulting in the deaths of Black men have ignited a national debate on policing policies. Given evidence that both police officers and Black men may be associated with threat, we examined the impact of perceived threat on support for reformed policing policies. Across three studies we found correlational evidence that perceiving police officers as threatening predicts increased support for reformed policing practices (e.g., limiting the use of lethal force and matching police force demographics to those of the community). In contrast, perceiving Black men as threatening predicted reduced support for policing policy …

Rapid Cortisol And Testosterone Responses To Sex-Linked Stressors: Implications For The Tend-And-Befriend Hypothesis, Jennifer Byrd-Craven, Jessica L. Calvi, Shelia M. Kennison

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Current evolutionary theories regarding the nature of hormonal responses to a variety of salient social stimuli are incomplete in yielding evidentiary support for their assertions. This study offers more nuanced evidence for the Tend-and- Befriend model of sex differences in responses to social stimuli. Participants were randomly assigned to a mortality salience prime or a control condition prior to viewing a video of an out-group threat or a video of infants crying. Cortisol and testosterone responses were assessed. The results showed that in mortality salience conditions, females showed significantly higher cortisol responses to infants crying compared to males. Further, in …

Neural Processing Of Emotional Musical And Nonmusical Stimuli In Depression, Rebecca J. Lepping, Ruth Ann Atchley, Evangelia Chrysikou, Laura E. Martin, Alicia A. Clair, Rick E. Ingram, W. Kyle Simmons, Cary R. Savage

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Background Anterior cingulate cortex (ACC) and striatum are part of the emotional neural circuitry implicated in major depressive disorder (MDD). Music is often used for emotion regulation, and pleasurable music listening activates the dopaminergic system in the brain, including the ACC. The present study uses functional MRI (fMRI) and an emotional nonmusical and musical stimuli paradigm to examine how neural processing of emotionally provocative auditory stimuli is altered within the ACC and striatum in depression.

Method Nineteen MDD and 20 never-depressed (ND) control participants listened to standardized positive and negative emotional musical and nonmusical stimuli during fMRI scanning and gave …

Voxel-Based Morphometry Reveals Brain Gray Matter Volume Changes In Successful Dieters, Robyn A. Honea, Amanda N. Szabo-Reed, Rebecca J. Lepping, Rodrigo Perea, Florence Breslin, Laura E. Martin, William M. Brooks, Joseph E. Donnelly, Cary R. Savage

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Objective: To compare regional brain volume predictors of percent weight loss (WL) in dieters with obesity (DwO) and in the same participants categorized as “successful” (≥7% WL) or “unsuccessful” dieters (

Decline In Ethical Concerns About Reproductive Technologies Among A Representative Sample Of Us Women, Arthur L. Greil, Kathleen S. Slauson-Blevins, Karina M. Shreffler, Katherine M. Johnson, Michele Lowry, Andrea R. Burch, Julia Mcquillan

Department of Sociology: Faculty Publications

Public awareness and utilization of assisted reproductive technology has been increasing, but little is known about changes in ethical concerns over time. The National Survey of Fertility Barriers, a national, probability-based sample of US women, asked 2031 women the same set of questions about ethical concerns regarding six reproductive technologies on two separate occasions approximately 3 years apart. At Wave 1 (2004–2007), women had more concerns about treatments entailing the involvement of a third party than about treatments that did not. Ethical concerns declined between Wave 1 and Wave 2, but they declined faster for treatments entailing the involvement of …

Dysphagia Management And Research In An Acute-Care Military Treatment Facility: The Role Of Applied Informatics, Nancy Pearl Solomon, Angela M. Dietsch, Katie E. Dietrich-Burns, Edda L. Styrmisdottir, Christopher S. Armao

Department of Special Education and Communication Disorders: Faculty Publications

Purpose: This report describes the development and preliminary analysis of a database for traumatically injured military service members with dysphagia. Methods: A multidimensional database was developed to capture clinical variables related to swallowing. Data were derived from clinical records and instrumental swallow studies, and ranged from demographics, injury characteristics, swallowing biomechanics, medications, and standardized tools (e.g.. Glasgow Coma Scale, Penetration-Aspiration Scale). Bayesian Belief Network modeling was used to analyze the data at intermediate points, guide data collection, and predict outcomes. Predictive models were validated with independent data via receiver operating characteristic curves. Results: The first iteration of the model (n …

Differential Effects Of Cdh23753a On Auditory And Vestibular Functional Aging In C57bl/6j Mice, Bruce E. Mock, Sarath Vijayakumar, Jessica Pierce, Timothy A. Jones, Sherri M. Jones

Department of Special Education and Communication Disorders: Faculty Publications

The C57BL/6J (B6) mouse strain carries a cadherin 23 mutation (Cdh23^753A, also known as Ahl), which affects inner ear structures and results in age-related hearing loss. The B6.CAST strain harbors the wild type Cdh23 gene, and hence, the influence of Ahl is absent. The purpose of the present study was to characterize the effect of age and gender on gravity receptor function in B6 and B6.CAST strains and to compare functional aging between auditory and vestibular modalities. Auditory sensitivity declined at significantly faster rates than gravity receptor sensitivity for both strains. Indeed, vestibular functional aging was …

Paleoparasitological Evidence Of Pinworm (Enterobius Vermicularis) Infection In A Female Adolescent Residing In Ancient Tehran (Iran) 7000 Years Ago, Niloofar Paknazhad, Gholamreza Mowlavi, Jean Dupouy Camet, Mohammad Esmaeili Jelodar, Iraj Mobedi, Mahsasadat Makki, Eshrat Beigom Kia, Mostafa Rezaeian, Mehdi Mohebali, Siamak Sarlak, Faezeh Najafi

Harold W. Manter Laboratory: Library Materials

Background: The Molavi street archeological site south of Tehran, Iran accidentally provided a unique opportunity for paleoparasitological studies in Iran. A female skeleton was unearthed and evaluated to be 7,000 years old. Soil samples were collected around the pelvic and sacrum bones.

Findings: Careful microscopic investigation of rehydrated soil samples revealed the presence of one Enterobius vermicularis egg attached to the skeleton sacral region.

Conclusion: The present finding likely represents the oldest evidence of a human pinworm infection in Asia.

Baylisascaris Larva Migrans, Kevin R. Kazacos

Harold W. Manter Laboratory of Parasitology: Faculty and Staff Publications

Zoonotic diseases, such as baylisascariasis, are receiving increasing attention as components of disease emergence and resurgence (Kazacos, 2001). Baylisascariasis is caused by the roundworm Baylisascaris procyonis and is one of the more recent zoonotic disease developments. This disease remains one of the least known and poorly understood zoonotic diseases, yet over the past several decades it has become widespread. It originated in wildlife species and is now well established as a human malady. Baylisascariasis is transmitted to humans via consumption of contaminated feces, and the role of wildlife (primarily raccoons) in this transmission process is becoming more clearly known and …

The Differentiation And Protective Function Of Cytolytic Cd4 T Cells In Influenza Infection, Deborah M. Brown, Anna T. Lampe, Aspen M. Workman

School of Biological Sciences: Faculty Publications

CD4 T cells that recognize peptide antigen in the context of class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL) play a role in chronic as well as acute infections, such as influenza A virus (IAV) infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections, such as human immunodeficiency virus, mouse pox, murine gamma herpes virus, cytomegalovirus, Epstein–Barr virus, and influenza among others. We now appreciate …